Seeking A Depersonalization Cure: 5 Treatments For DP/DR

DPDR tends to be chronic and affects between 1% and 2.4% of the population. Despite the prevalence of depersonalization in the general population, it is still assumed to be a rare condition by most clinicians[^11]:

Unfortunately, most psychiatrists are still trained to believe that DPD is extremely rare and that whenever depersonalization is present, it represents an irrelevant symptom stemming from a primary condition such as major depression, an anxiety disorder, or even impending psychosis.

My best guess is that depersonalization is a maladaptive response to stress. Excessive stress dysregulates your HPA axis and vagal tone and leads to sustained increases in cortisol.

Too much stress for too long and your body begins to adapt by down-regulating emotional reactivity as a protective measure. Sierra puts it best:

The condition is generated by an anxiety-triggered, ’hard-wired’ inhibitory response to threat.

This down-regulation of stress responsiveness leads to emotional numbing, anhedonia, and detachment. A similar phenomenon is observed in PSTD patients, where they exhibit cortisol levels lower than controls.

By contrast, depressed patients show elevated cortisol and C-reactive protein.

Fluoxetine was not demonstrated to be efficacious in treating depersonalisation disorder.

https://www.ncbi.nlm.nih.gov/pubmed/15876908?dopt=Abstract

Electro-dermal biofeedback

8 sessions

Schoenberg et al. 2012

Electrodermal biofeedback was not effective in increasing SCR (a physiological marker of emotional response) or in decreasing trait measures of depersonalization (CDS)

http://www.tandfonline.com/doi/abs/10.1080/15299732.2011.606742

Naloxone

120 mg/day (average)

Simeon et al. 2005

Average 30% reduction of symptoms with treatment, as measured by 3 validated dissociation scales

https://www.ncbi.nlm.nih.gov/pubmed/15876908

A number of drug and non-drug treatments have been tested in depersonalization sufferers. However, studies on depersonalization treatment efficacy have been mixed. For example, in one study fluoxetine (Prozac) was not more effective than placebo.

As such, there is no magic bullet for depersonalization. Medications that manipulate serotonin, gluatamate and opioid receptors show promise for treating depersonalization, though results have been inconsistent.

Some commonly proposed treatments include:

The anticonvulsant lamotrigine (Lamictal)

Opioid antagonists, .e.g, Naloxone

Transcranial magnetic stimulation (rTMS) or biofeedback

Tricyclic antidepressants like Clomipramine

Clomipramine, lamotrigine, and naloxone have been suggested by researchers as potential treatments for depersonalization disorder. More recently, repetitive transcranial magnetic stimulation (rTMS) is in vogue.

If you think about all the varying states of consciousness that humans can experience, depersonalization is one of the most terrifyingly disconcerting and bizarre. Unfortunately, there's no "gold standard treatment" and finding a medicine or regimen that works may take lots of trial and error.

What is DPDR?

DPDR stands for depersonalization-derealization disorder.

Depersonalization/derealization is a dissociative disorder. Other dissociative disorders include:

dissociative amnesia

dissociative fugue

dissociative identity disorder

dissociative disorder not otherwise specified (NOS)

Depersonalization, or derealization, occurs when one feels separated from one's body. It's almost as if you are observing the environment like a detached outsider.

Depersonalization is equally prevalent among men and women and usually occurs without any prior history of identity disorders.

There's overlap between depersonalization and anhedonia or the inability to experience pleasure.

What Triggers Depersonalization?

Depersonalization tends to follow periods of intense anxiety, stress, panic, and depression. DPDR can also be drug-induced (e.g., due to an adverse reaction to hallucinogens).[^1]

The condition usually begins in adolescence and follows a persistent course. It many cases depersonalization produces severe subjective distress and can become incapacitating.

Limbic system suppression in emotional responses has been implicated in depersonalization.

Symptoms of Depersonalization

Patients with depersonalization complain of four symptoms:

detachment from their bodies

feelings of estrangement from personal memories

numbing of emotional responses and dream-like states

the feeling that the external world seems unreal[^2]

Co-Morbidities

Depersonalization co-occurs with a variety of other disorders. Depersonalization tends to evade diagnosis due to a high rate of comorbidity.

Some disorders that co-occur with depersonalization include anxiety, depression, borderline personality disorder, and obsessive-compulsive disorder.[^1]

Misdiagnosis of depersonalization may also be high because some psychologists believe it is a secondary effect of other disorders.[^2]

Depersonalization in the context of depression may indicate a marker of resistance to pharmacotherapy.[^11]

Drugs That Treat Depersonalization

Several classes of drugs including amphetamines[^10], barbiturates, selective serotonin re-uptake inhibitors (SSRIs), and antipsychotics have been tested as treatment options. In several studies, SSRIs have shown some promising effects in treatment. However, findings have been disappointingly inconsistent.[^2]

The visual derealization effect likely arises from changes in the brain’s occipital and temporal circuitry, while symptoms of bodily detachment are attributed to parietal dysfunction.[^4]

Dampened emotional reactivity is linked to inhibition of the amygdala, a component of the limbic system that plays a key role in mediating emotional responses.[^4]

Serotonergic Drugs For Depersonalization

Treatments targeting serotonergic pathways may be viable for depersonalization.

Psilocybin and cannabis have both been found to produce feelings of time distortion and memory impairment.[^2]

The psychoactive effects of cannabis are largely related to activity at cannabinoid receptors. But THC also affects serotonergic pathways. Cannabis-induced depersonalization is dose-dependent. Other marked serotonin agonists such as meta-chlorophenylpiperazine, lysergic acid diethylamide, and ecstasy reportedly elicit depersonalization.

One study administered clomipramine, an SSRI, to eight patients suffering from depersonalization disorder.

After clomipramine treatment, two patients reported drastic improvement in their symptoms. These patients did not have any co-morbid mental illness, such as depression.[^2] Nevertheless, the singular use of SSRI medication has not been suggested as monotherapy for depersonalization.

Role For Glutamate?

Other research has shown the links between glutamate and depersonalization.

Ketamine

Sub-anesthetic doses of ketamine are well known to elicit effects similar to depersonalization. Researchers have investigated this phenomenon with neuroimaging (MRI) and discovered similarities between responses to ketamine and patients with depersonalization [^5].

Ketamine releases glutamate after blockade of the NMDA receptors, leading to glutamate’s interaction at other receptor sites.[^3]

Lamictal (Lamotrigine)

Lamotrigine - an anticonvulsant - may mitigate the effects of ketamine-induced depersonalization.

Lamotrigine was given to 32 patients with depersonalization disorder who were also previously prescribed SSRIs. Lamotrogine reduced depersonalization symptoms by over 30% in 18 patients, as measured by the Cambridge Depersonalization Scale.[^3] One confound of the study was the prior prescription of SSRIs.

Somer et al. note in their meta-analysis that:

Data on lamotrigine for DPRD was inconsistent with one trial indicating that lamotrigine was not significantly better than placebo when applied as a singular treatment for DPRD, and one trial showing a statistically significant difference in improvement (i.e., 50% reduction in the CDS) compared placebo.

Apart from serotonin and glutamate, drugs that target the opioid system have also been tested.

Opioids and Emotional Numbing

The emotional numbing observed in depersonalizaton may be an opioid-mediated phenomenon.

The endogenous opioid system is responsible for mediating pain relief in response to stress. For example, the "runner's high" has been attributed to endogenous opioid like endorphin.

Anxiety and depression are believed to alter the endogenous opioid system.

A particular class of opioid agonists induce effects that are reminiscent of depersonalization. As such, researchers have long speculated that certain opioid antagonists like naloxone may be viable treatments for depersonalization. These assumptions have been born out in clinical studies. High-dose naloxone reduced the effects of long-term depersonalization and border-line personality disorder.[^4]

Naltrexone, another opioid antagonist, was prescribed to 14 patients with depersonalization disorder over a six- or eight-week period. Three patients reported a ~70% reduction in symptoms. A reduction of 30% was reported for the entire group.[^6]

Non-Drug Treatments

Non-pharmacological approaches have been tested for depersonalization.

Repetitive transcranial magnetic stimulation (rTMS) has produced encouraging results. rTMS involves altering the electrical activity of the brain using a magnetic field. A handful of case studies in the late 90s showed promising results after rTMS was used on patients who were refractory to pharmacological treatment.

Seven patients received 20 sessions of rTMS over the course of 10 weeks. One session consisted of TMS at 1 Hz frequency that lasted 15 minutes. TMS was delivered to the ventrolateral prefrontal cortex (VLPFC).

Treatment reduced scores on the Cambridge Depersonalization Scale by 44%, on average. Only one patient failed to respond. The study authors speculated that symptoms might further improve on the Cambridge Depersonalization Scale with more rTMS sessions.

Improvement was also noted on the Beck Depression Inventory and Beck Anxiety Inventory, though the results failed to reach statistical significance.[^7]

Summary

Several pharmacological approaches have been tested for the treatment of depersonalization. rTMS is a novel treatment that calls for larger, randomized trials. Though scientists have used rTMS mainly in patients refractory to pharmaceuticals, the treatment shows promise as a first-line approach for alleviating depersonalization.